Orexins

Orexins in the Body

Orexin-producing neurons receive signals from the body, the emotions, and the environment, then release orexins that affect the entire central nervous system Trusted Source National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source . In fact, orexins appear to play such diverse roles in the body that researchers contend that we’re only just beginning to understand their importance.

It’s believed that orexins are primarily excitatory, which means that they cause other neurons to become active and start sending their own signals. Among the many functions of orexins discovered, they appear to play an important role in sleep, energy metabolism, and mood.

Recent research has offered a hypothesis that attempts to explain all of the seemingly diverse roles of orexins in the body Trusted Source National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source . This hypothesis suggests that orexins regulate behavior during times of physiological need, exposure to threats, and opportunities for reward.

Understanding the many effects of orexins in the body is exciting and valuable. Research in this area increases our understanding of the human body. It also offers promising new ways to treat a multitude of conditions, including insomnia, narcolepsy, depression, and even obesity.

Sleep and Arousal

It’s hypothesized that a primary role of orexins is to control sleep and arousal, and the neurons that release orexins are most active during the day. To keep us awake, these neuropeptides stimulate other neurons to release neurotransmitters that promote alertness, such as dopamine, serotonin, and norepinephrine.

Without enough orexins, the body has a hard time staying awake and alert. People diagnosed with type 1 narcolepsy have an 85% to 95% reduction in the number of neurons that produce orexins Trusted Source National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source . This loss of orexin-producing neurons leads to the symptoms of narcolepsy, including excessive daytime sleepiness, sleep paralysis, hallucinations, and cataplexy.

While weight gain is not a symptom of narcolepsy, people with this condition are more likely to be overweight Trusted Source National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source . Research suggests that the link between narcolepsy and weight gain may be related to orexin’s role in regulating physical activity.

Stress, Physical Activity, and Obesity

Orexins are important in the body’s response to stress Trusted Source National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source . Taking in signals from the environment, orexin-producing neurons respond to pressure by exciting other neurons that increase heart rate and blood pressure, helping the body transition from a resting state to one where it’s ready to respond and move.

With fewer chemical signals to motivate responses, deficiencies in orexins are linked to physical inactivity and obesity. Animal research has shown that mice who lose their orexin-producing neurons are less physically active, have decreased energy metabolism Trusted Source National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source , and are more likely to develop obesity and diabetes, even when they consume fewer calories.

Mood and Memory

Orexins also excite neurons important in regulating mood. Having too much or too little orexin activity has been linked to depression Trusted Source SpringerLink SpringerLink provides researchers with access to millions of scientific documents from journals, books, series, protocols, reference works, and proceedings. View Source and other mental health conditions, such as anxiety, panic disorder, addictions, and post-traumatic stress disorder.

These neuropeptides also impact mood through their function in a part of the brain called the hippocampus. Orexins encourage the creation of new neurons in the hippocampus, which is important in learning, memory, and spatial abilities. Without sufficient orexins, people can develop problems with learning and memory.

Sleep Aids Targeting Orexins

Since orexins stimulate wakefulness, blocking the effects of these neuropeptides is one way to treat some sleep disorders. Dual orexin receptor antagonists (DORAs) are a new type of prescription sleep aid that targets the body’s orexin system. These medications work by acting as orexin receptor antagonists, meaning that they block the effects of orexins in the body, reduce the drive to stay awake, and facilitate sleep.

Two types of DORAs are currently approved by the Food and Drug Administration (FDA) for the treatment of insomnia in adults: suvorexant Trusted Source National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source and lemborexant Trusted Source National Library of Medicine, Biotech Information The National Center for Biotechnology Information advances science and health by providing access to biomedical and genomic information. View Source . Newer DORAs are still in development.

DORAs differ from other types of sleep aids because they affect different systems in the body. Over-the-counter sleep aids, like diphenhydramine and melatonin, cause sedation or help to regulate the body’s circadian rhythm. Prescription sleep aids promote sleep in other ways, like targeting GABA receptors in the brain, and may come with undesirable side effects, like memory issues, behavior changes, and even hallucinations.

Researchers hope that, by targeting the body’s orexin system, DORAs may be effective with fewer side effects. In fact, both FDA-approved DORAs have been shown to improve sleep quality in people with insomnia and the most common side effect associated with their use is drowsiness. They may also improve sleep architecture, and have been used to improve delirium in hospitalized patients.

While DORAs offer a promising new approach to treating insomnia, they’re not appropriate for everyone. Before taking any medication, be sure to consult with your doctor or a sleep specialist. For many people with insomnia and other sleep issues, it’s helpful to start by focusing on behavior changes, like improving your sleep hygiene, before considering medication.

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